1. MENOPAUSAL HORMONAL TREATMENT AND BREAST CANCER RISK PROF DR H DEPYPERE Gynaecologische oncologie en borstkliniek, Universitair Ziekenhuis, Gent

2. Sixty procent of women have vasomotor complaints Cochrane data base of randomised trials indicates hormonal replacement is the most effective treatment to treat vasomotor symptoms A small increase in breast cancer will deter women from taking HRT

3. Womens perceptions of their greatest health problems Mosca L et al Arch Fam Med 2000;9:506-515

5. Age at menarche3 menarche before 11 age at menopause2 menopause after 54 age at first full pregnancy3 first child in early 40s family history >2 first degree when young previous benign disease4-5 atypical hyperplasia cancer in other breast >4 diet1.5 high sat fat intake BMIpremenopausal 0.7 BMI>35 postmenopausal2 BMI>35 alcohol1.3 hrt1.35 hers, NHS, WHI

7. Estrogen only Safer progestogens Serm :MORE trial STAR trial CORE trial

8. Estrogens are not associated with an increase in breast cancer incidence (WHI : JAMA 2002;288:321-333; Olsson et al, Cancer, 2003, 97;1387-1392). Latest results of WHI suggest a significant reduction. Million Women Study does suggest an increase in breast cancer in estrogen only treatment (Lancet 2003;362:419-427). This is also observed in E3N study Int J Cancer 2005;114:448-454). Dahors study indicates a very small increase. INFLUENCE OF ET ON BREAST CANCER INCIDENCE

9. Estrogen only WHI RR 0.77 NHS - duration ? 28 835 women with hysterectomy BMI 25 never 781.001481.00 <5 y451.03 (0.69-1.52) 540.96 (0.96-1.33) 5-9.9781.17 (0.84-1.62) 660.74 (0.55-1.00) 10-14.9941.18 (0.86-1.62) 940.97 (0.74-1.28) 15-19.9661.36 (0.97-1.92) 631.11 (0.82-1.51) >20801.77 (1.26-2.48) 651.25 (0.91-1.71)

10. Estrogen only Safer progestogens Serm :MORE trial STAR trial CORE trial

11. Hers I study (RR : 1.38 (0.82-2.31; p =0.22)) WHI (RR :1.26 (1.00-1.59)) conform : Nurses health study and Lancet 97 meta analysis (RR :1.35 (1.21-1.49)) This is also observed in E3N study for synthetic progestogens and not for natural progesterone. In WHI only significant increase in breast cancer after more than 5 years of intake of EPT INFLUENCE OF EPT ON BREAST CANCER INCIDENCE

12. Prospective study Prospective study 54.584 postmenopausal women 54.584 postmenopausal women 5,8 years follow-up 5,8 years follow-up 29.420 HRT users (54%) 29.420 HRT users (54%) 12% E2 alone 12% E2 alone 88% EP combined 88% EP combined 948 invasive breast cancer 948 invasive breast cancer

13. Oral estrogens + Synthetic progestogen + micronized progesteron + Synthetic progestogen RR = 1.3 (1.1-1.5) RR = 0.9 (0.7-1.2) RR = 1.4 (1.2-1.7) RR = 1.5 (1.1-1.9) Cutan. estrogens estrogens + progestatogen To small number to compare

15. Breast cancer risk according to progestogen type and estrogen dose 1 mg NETA 51-54 RR 1.3; 55-59 RR 2.2; 60-64 RR 2.7; 65-69 RR 3.0 0.5 mg NETA no significant increase in any age group;

16. Dahors : Danish Sex Hormones register Study 4 242 334 women years 12 831 breast cancers deaths per 100 women years never users:5.9 ever users :4.5 current users :2.9

17. Estrogen only Safer progestogens Serm :MORE trial STAR trial CORE trial

18. Cauley J, et al. Breast Cancer Res Treatment. 2001;65:125-134 Years 0.0 2.0 012345 Raloxifene 1.9 per 1000 woman-years Placebo 5.3 per 1000 woman-years % of Randomized Patients RR = 0.38 (95% CI = 0.24-0.58)* Effect of Raloxifene on Breast Cancer Incidence MORE Trial - 48 Months Total Cases = 77 *P<.001 1.0

19. 7705 postmenopausal women 10.5 per 1000 women in control arm. Reduction by 76 % with raloxifen. This implicates a reduction of 2.52 breast cancers per 1000 women. Only ER rec positive tumors are prevented. Raloxifen

20. 3510 women receiving raloxifene 60 mg/d vs 1703 women receiving placebo from more that continue in core. ER positive invasive breast cancers reduced 66 % (RR 0.34 CI : 0.18-0.66). No difference in ER negative cancers. Absolute numbers 1.4 cancers per 1000 women per year vs 4.2 cancers. CORE - Continuing Outcomes Relevant to Evista

21. Mammografie voor en na behandeling met Livial ® Vrouwen onder CEE/MPA Vrouwen onder CEE/MPA Dezelfde vrouwen na 1 jaar behandeling met Livial Valdivia & Ortega 2000 Clin Drug Invest 20:101-107

22. Practical guidelines A small increase in breast cancer will deter women from taking HRT. Small increase in breast cancer with EPT formulations. Importance of progestogen. Increase with ET after 20 years. The combination with mirena is an interesting option. Serm concept is an interesting field of new development. Tibolone data from liberate will be disclosed next year.